N2O for Acute Suicidality and Depression in the ED

Investigators are conducting this double-blind, randomized control trial (RCT), to compare inhaled N2O+ treatment as usual (TAU) versus inhaled placebo+TAU; demonstrating the feasibility and tolerability of the intervention in an emergency department (ED) setting on an acutely suicidal population.

Inclusion Criteria:Patients 18-65 years of age, acutely suicidal, presenting to the adult emergency department with documented history of non-psychotic major depressive disorder.Exclusion Criteria:Current psychotic or catatonic symptoms as determined by the hospital care team.Unable or unwilling to give consent for study participation (ability to provide consent will be established by treating physician)Lifetime DSM-V (medical history) diagnoses of schizophrenia, schizoaffective disorders, bipolar disorder, obsessive-compulsive disorder, and panic disorders.Meets current DSM-V substance use disorder of greater than mild severity (other than nicotine or marijuana)Significant pulmonary disease and/or requiring supplemental oxygen.Administration of other NMDA-receptor antagonist treatment (e.g., ketamine) within two weeks of entry into study.Contraindications for N2O (pneumothorax, bowel obstruction, middle ear occlusion, elevated intracranial pressure)Chronic cobalamin and/or folate deficiency treated with folic acid or vitamin B12.Women who are pregnant or breastfeedingAny other factor that in the investigators' judgment may affect patient safety or compliance.